A smart hydrogel-based time bomb triggers drug release mediated by pH-jump reaction

Abstract

We demonstrate a timed explosive drug release from smart pH-responsive hydrogels by utilizing a phototriggered spatial pH-jump reaction. A photoinitiated proton-releasing reaction of o-nitrobenzaldehyde (o-NBA) was integrated into poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide) (P(NIPAAm-co-CIPAAm)) hydrogels. o-NBA-hydrogels demonstrated the rapid release of protons upon UV irradiation, allowing the pH inside the gel to decrease to below the pK a value of P(NIPAAm-co-CIPAAm). The generated protons diffused gradually toward the non-illuminated area, and the diffusion kinetics could be controlled by adjusting the UV irradiation time and intensity. After irradiation, we observed the enhanced release of entrapped L-3,4-dihydroxyphenylalanine (DOPA) from the gels, which was driven by the dissociation of DOPA from CIPAAm. Local UV irradiation also triggered the release of DOPA from the non-illuminated area in the gel via the diffusion of protons. Conventional systems can activate only the illuminated region, and their response is discontinuous when the light is turned off. The ability of the proposed pH-jump system to permit gradual activation via proton diffusion may be beneficial for the design of predictive and programmable devices for drug delivery.

Photo-triggered microgel aggregation using o -nitrobenzaldehyde as aggregating power source

“…As reported previously, o ‐nitrobenzaldehyde (NBA) reacts to UV light irradiation and releasing proton. As a result, the pH value of the NBA solution decreases.…”

“…Meanwhile, it is known that o ‐nitrobenzaldehyde (NBA) exhibits photo‐triggered reaction in water . By UV light irradiation, NBA releases proton of its aldehyde substituent, and pH value of the solution is decreased.…”

A Photoinduced Nanoparticle Separation in Microchannels via pH-Sensitive Surface Traps

“…26,27 The proton-releasing reactions are important and useful for not only investigating dynamics of pH-dependent phenomena such as protein folding kinetics, but also on-demand changing the proton concentration quickly in solution. 30 Fig.…”

“…When a photo-mask was utilized to limit the UV irradiation to a specific channel region, we were able to restrict the particle separation to only the exposed region. 26, 27 …”

Photo-induced Control of Smart Polymer Systems via pH Jump Reaction

“…The NBA-integrated gel was also successfully employed for the controlled release of entrapped dextran, where dextran was successfully entrapped into the gel and then released into water in a controlled manner under 365 nm UV illumination. This system shows significant promise as a smart platform for triggered and programmed delivery of drugs [19]. Fig.3.…”